The clinical use of dapsone has expanded over the last decade. Dapsone is now the drug of choice for certain autoimmune-associated disorders such as dermatitis herpetiformis, and is an important component of prophylaxis and chemotherapy for opportunistic infections, such as P. carnii pneumonia, in AIDS patients. In both situations, dapsone's hemotoxicity; viz, methemoglobinemia and hemolytic anemia, are dose limiting in therapy. Over the life of this grant, we have used a rat model to identify the hemotoxic metabolites (N-hydroxydapsone (DDS-NOH) and N-acetyl-N- hydroxydapsone (MADDS-NOH)) of the drug and to gain insight into the mechanism underlying the hemolytic response. We now propose to test the hypothesis that the insight gained with the rat model can be used to reduce the severity of dapsone-induced hemotoxicity in humans and hence, improve the therapeutic ratio of the drug.